chr6-101516967-T-C

Position:

• chr6-101516967-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021956.5(GRIK2):​c.116-104982T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,134 control chromosomes in the GnomAD database, including 1,344 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1344 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

Genes affected

GRIK2 (HGNC:4580): (glutamate ionotropic receptor kainate type subunit 2) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing at multiple sites within the first and second transmembrane domains, which is thought to alter the structure and function of the receptor complex. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. Mutations in this gene have been associated with autosomal recessive cognitive disability. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.116-104982T>C		intron_variant		ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9	c.116-104982T>C		intron_variant		5	NM_021956.5	ENSP00000358130	P4

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18827 AN: 152016 Hom.: 1342 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.0709

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.118

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.124 AC: 18851 AN: 152134 Hom.: 1344 Cov.: 32 AF XY: 0.120 AC XY: 8896 AN XY: 74376

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0897

Gnomad4 EAS AF: 0.0426

Gnomad4 SAS AF: 0.0863

Gnomad4 FIN AF: 0.0709

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.116

Alfa AF: 0.111 Hom.: 1294

Bravo AF: 0.129

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7760831; hg19: chr6-101964843;